45,998 research outputs found
A temporal logic approach to modular design of synthetic biological circuits
We present a new approach for the design of a synthetic biological circuit
whose behaviour is specified in terms of signal temporal logic (STL) formulae.
We first show how to characterise with STL formulae the input/output behaviour
of biological modules miming the classical logical gates (AND, NOT, OR). Hence,
we provide the regions of the parameter space for which these specifications
are satisfied. Given a STL specification of the target circuit to be designed
and the networks of its constituent components, we propose a methodology to
constrain the behaviour of each module, then identifying the subset of the
parameter space in which those constraints are satisfied, providing also a
measure of the robustness for the target circuit design. This approach, which
leverages recent results on the quantitative semantics of Signal Temporal
Logic, is illustrated by synthesising a biological implementation of an
half-adder
A Method to Identify and Analyze Biological Programs through Automated Reasoning.
Predictive biology is elusive because rigorous, data-constrained, mechanistic models of complex biological systems are difficult to derive and validate. Current approaches tend to construct and examine static interaction network models, which are descriptively rich but often lack explanatory and predictive power, or dynamic models that can be simulated to reproduce known behavior. However, in such approaches implicit assumptions are introduced as typically only one mechanism is considered, and exhaustively investigating all scenarios is impractical using simulation. To address these limitations, we present a methodology based on automated formal reasoning, which permits the synthesis and analysis of the complete set of logical models consistent with experimental observations. We test hypotheses against all candidate models, and remove the need for simulation by characterizing and simultaneously analyzing all mechanistic explanations of observed behavior. Our methodology transforms knowledge of complex biological processes from sets of possible interactions and experimental observations to precise, predictive biological programs governing cell function
Efficient parameter search for qualitative models of regulatory networks using symbolic model checking
Investigating the relation between the structure and behavior of complex
biological networks often involves posing the following two questions: Is a
hypothesized structure of a regulatory network consistent with the observed
behavior? And can a proposed structure generate a desired behavior? Answering
these questions presupposes that we are able to test the compatibility of
network structure and behavior. We cast these questions into a parameter search
problem for qualitative models of regulatory networks, in particular
piecewise-affine differential equation models. We develop a method based on
symbolic model checking that avoids enumerating all possible parametrizations,
and show that this method performs well on real biological problems, using the
IRMA synthetic network and benchmark experimental data sets. We test the
consistency between the IRMA network structure and the time-series data, and
search for parameter modifications that would improve the robustness of the
external control of the system behavior
Learning and Designing Stochastic Processes from Logical Constraints
Stochastic processes offer a flexible mathematical formalism to model and
reason about systems. Most analysis tools, however, start from the premises
that models are fully specified, so that any parameters controlling the
system's dynamics must be known exactly. As this is seldom the case, many
methods have been devised over the last decade to infer (learn) such parameters
from observations of the state of the system. In this paper, we depart from
this approach by assuming that our observations are {\it qualitative}
properties encoded as satisfaction of linear temporal logic formulae, as
opposed to quantitative observations of the state of the system. An important
feature of this approach is that it unifies naturally the system identification
and the system design problems, where the properties, instead of observations,
represent requirements to be satisfied. We develop a principled statistical
estimation procedure based on maximising the likelihood of the system's
parameters, using recent ideas from statistical machine learning. We
demonstrate the efficacy and broad applicability of our method on a range of
simple but non-trivial examples, including rumour spreading in social networks
and hybrid models of gene regulation
Dynamical complexity of discrete time regulatory networks
Genetic regulatory networks are usually modeled by systems of coupled
differential equations and by finite state models, better known as logical
networks, are also used. In this paper we consider a class of models of
regulatory networks which present both discrete and continuous aspects. Our
models consist of a network of units, whose states are quantified by a
continuous real variable. The state of each unit in the network evolves
according to a contractive transformation chosen from a finite collection of
possible transformations, according to a rule which depends on the state of the
neighboring units. As a first approximation to the complete description of the
dynamics of this networks we focus on a global characteristic, the dynamical
complexity, related to the proliferation of distinguishable temporal behaviors.
In this work we give explicit conditions under which explicit relations between
the topological structure of the regulatory network, and the growth rate of the
dynamical complexity can be established. We illustrate our results by means of
some biologically motivated examples.Comment: 28 pages, 4 figure
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